Ultrasound Evaluation of the Fetal Central Nervous System

Ventriculomegaly

Enlargement of the lateral cerebral ventricles, commonly referred to as ventriculomegaly ( Fig. 9-5 ), is a nonspecific marker of abnormal brain development. The presence of normal fetal lateral ventricles on ultrasound examination decreases the risk of a CNS anomaly, whereas detection of ventriculomegaly increases the risk that a significant malformation is present. Although many different approaches to the evaluation of the lateral ventricles have been proposed, measurement of the width of the atrium (or posterior horn) of the lateral ventricle is currently favored. In a normal fetus, the measurement of the lateral ventricle should be less than 10 mm between 15 and 40 weeks’ gestation. In most fetuses with significant ventricular enlargement, the ventricles are symmetrically affected whereas cases with milder degrees of ventriculomegaly are more commonly unilateral. Male fetuses have a slightly larger atrial size than female fetuses. A study by Patel and associates demonstrated that atrial size demonstrated a near-normal distribution, with mean size for all subjects 6.1 mm ± 1.3 (standard deviation [SD]). When separated by sex, the mean atrial diameter of 122 female fetuses was 5.8 mm ± 1.3, and the mean atrial diameter of 97 male fetuses was 6.4 mm ± 1.3. The difference in mean size was statistically significant ( P < 0.005). Thus, a ventricular atrial measurement of 10 to 11 mm will have more significance in a female fetus than in a male fetus.

A ventricular atrial width of more than 15 mm indicates severe ventriculomegaly . This is almost always associated with an intracranial malformation, although the outcome is variable and depends largely upon the underlying cause. The available studies suggest that fetuses with isolated severe ventriculomegaly have an increased risk of perinatal death and a probability of severe long-term neurologic sequelae in at least 50% of survivors.

An intermediate value of the atrial width, 10 to 15 mm, is commonly referred to as mild ventriculomegaly and is less frequently associated with significant CNS anomalies, although it can be seen with ACC and open neural tube defects. Mild ventriculomegaly is also associated with chromosomal aberrations: the risk of trisomy 21 is increased 3.8 times when ventricular enlargement is an isolated finding. Fetal infections, such as cytomegalovirus (CMV), may result in ventricular enlargement, although usually other sonographic abnormalities are also present (areas of focal cerebral increased echogenicity, microcephaly, and porencephaly). When mild ventriculomegaly is isolated, and associated anomalies are absent, most infants are asymptomatic after birth. However, several reports have indicated that some fetuses are found to have severe CNS anomalies in advanced gestation or after birth (hydrocephalus, white matter injury, and cortical plate abnormalities), and some studies have reported an increased risk of neurologic compromise. Studies reporting on the prognosis of mild ventriculomegaly have been limited by the lack of standardized follow-up protocols and difficulty in defining “normal” neurologic outcome. However, most fetuses with mild ventriculomegaly will have a normal outcome, whereas about 10% demonstrate neurodevelopmental abnormalities of variable types and magnitude.

When mild ventriculomegaly is encountered, it is important to rule out associated anomalies. A targeted sonographic survey of fetal anatomy should be performed, with particular attention to details of the CNS. Fetal diagnostic testing for aneuploidy should be offered, and chromosomal microarray should be considered. Detailed ultrasound assessment of the CNS may be enhanced by transvaginal scanning, particularly if the fetus is in cephalic presentation. There is some debate as to whether fetal MRI is indicated in all cases of apparently isolated ventriculomegaly. This technique may provide significant diagnostic information, as it allows more detailed assessment of the developing fetal brain and detection of disorders of sulcation, cortical malformations, and migrational abnormalities. In continuing pregnancies in which mild ventriculomegaly has been identified, standard obstetric management is recommended.

Neural Tube Defects

The incidence, cause, and recurrence risk of neural tube defects are reported in Tables 9-1 through 9-3 . There are several different forms of neural tube defects.

Anencephaly is characterized by the absence of the cranial vault and telencephalon. The diagnosis is made by ultrasound in the second and third trimesters and relies upon demonstration of the absence of the cranial vault. In addition, most cases can be confidently identified by 11 to 13 weeks’ gestation. At this time, the fetal head can be recognized as overtly abnormal owing to lack of an ossified calvarium ( Fig. 9-6 ). The terms acrania and exencephaly have also been used to describe this appearance; these represent early stages in the development of anencephaly. The outcome of anencephaly is uniformly fatal.

Spina bifida can occur in open as well as closed forms. Open spina bifida is characterized by a full-thickness defect of the skin, underlying soft tissues, and vertebral arches, with exposure of the neural canal. These defects may vary considerably in size, with the lumbar and sacral areas most frequently affected. Leakage of cerebrospinal fluid through the defect results in an increased concentration of alpha-fetoprotein (AFP) and acetylcholinesterase in the amniotic fluid and maternal serum, and measurement of maternal serum and amniotic fluid AFP can be used to screen for neural tube defects.

Open spina bifida can be identified sonographically by demonstrating the opening of the neural tube and the defect in the vertebrae (splaying outward of the posterior elements) as well as the overlying soft tissues ( Fig. 9-7 ). A cyst formed by the fusion of the malformed cord and meninges (myelomeningocele) is usually found. In a minority of cases, there is no covering membrane (myelocele). The diagnosis of a neural tube defect may be difficult and requires meticulous scanning. Examination of the fetal head is of great utility, as open spina bifida is consistently associated with characteristic and readily recognizable intracranial lesions. Leakage of cerebrospinal fluid leads to displacement of the cerebellum and medulla oblongata through the foramen magnum inside the upper cervical canal (Chiari type II or Arnold-Chiari malformation). Sonographically, this results in small head measurements in the midtrimester, as well as obliteration of the cisterna magna; small size and abnormal shape of the cerebellum (banana sign), which is located deep in the posterior fossa; scalloping of the frontal bones (lemon sign); and ventriculomegaly. Another characteristic abnormality is a “pointed” appearance of the occipital horns of the lateral ventricle. The occipital point is a common supratentorial feature of the Chiari II malformation. It is seen more commonly in fetuses younger than 24 weeks and in those with normal-sized ventricles. Interestingly, it is seen as commonly among fetuses with mild posterior fossa deformations as in those with more severe distortions (see Fig. 9-7 ). Overall, the detection rate of open spina bifida at the midtrimester obstetric sonogram has been reported to be at least 90%. Abnormalities of the posterior fossa and lateral ventricles have also been described at 11 to 13 weeks’ gestation, but the diagnostic accuracy of these findings to screen for spina bifida is still being assessed.

Several other neural axis abnormalities are frequently associated with myelomeningocele and Chiari II malformation, both intracranial and extracranial. These abnormalities are known to exist in the presence of myelomeningocele, and thus, when observed, the fetus should not be considered to have “multiple anomalies” ( Table 9-4 ).

There is a correlation between the location (vertebral level) and extension of the spinal lesion and the neurologic outcome. In general, lower and smaller defects result in less severe neurologic compromise. The level of the bony spinal lesion can be determined by counting the affected vertebrae either from the most distal vertebra (in the second trimester fetus, the lowest ossified vertebra is S4) or from the rib cage (which ends at T12). Antenatal ultrasound assessment correlates reasonably well with postnatal assessment (75%), and MRI has been found to add little to determination of the bony level of the defect. However, it is not possible to precisely predict motor function, morbidity, or developmental milestones. Of note, the degree of ventricular enlargement does correlate with the need for postnatal shunting.

Antenatal counseling after detection of fetal spina bifida is complex and should involve a multidisciplinary team. Postnatal hydrocephalus requiring shunting, causing incontinence, and resulting in motor weakness requiring wheelchair use is common. Options for management of an affected pregnancy include termination, expectant management with postnatal repair, and in utero surgical repair (see Chapter 24 ). The benefit of cesarean delivery to improve neurologic outcome of infants with open spina bifida is uncertain.

Closed spina bifida is characterized by a vertebral defect (schisis) covered by skin. Most defects are small, involving only a few vertebral segments, and the classic intracranial signs (lemon-shaped calvarium, banana-shaped cerebellum, ventriculomegaly) are absent ( Fig. 9-8 ). As a consequence, the sonographic diagnosis of closed spina bifida is difficult and in practice is only possible in those cases that are associated with a subcutaneous mass, such as a meningocele or lipoma overlying the bony defect. The outcome of closed spina bifida is difficult to predict. These infants do not develop Arnold-Chiari malformation or hydrocephalus. However, those with subcutaneous masses may suffer from neurologic sequelae, including weakness or paralysis of the lower extremities and incontinence, usually as a consequence of tethering or compression of the spinal cord.

The term cephalocele is used to describe a protrusion of intracranial contents through a bony defect of the skull. Most commonly, these lesions arise from the midline, in the occipital area; they arise less commonly from the parietal or frontal bones. Encephaloceles are characterized by the presence of brain tissue in the lesion. When only meninges protrude, the term cranial meningocele is used. Cephaloceles often cause impaired cerebrospinal fluid circulation and hydrocephalus, and massive encephaloceles may be associated with microcephaly. Associated anomalies are frequent ( Table 9-5 ). Fetal cephaloceles are suspected when a paracranial mass is seen on sonography ( Fig. 9-9 ). The diagnosis of encephalocele is typically straightforward, as the presence of brain tissue inside the sac is striking on ultrasound images, although distinguishing a cranial meningocele from soft tissue edema or a cystic hygroma of the neck may be difficult. The diagnosis of cephalocele is favored when it is possible to demonstrate a bony defect in the cranial vault or associated cerebral abnormalities, such as ventriculomegaly. The pediatric literature suggests that the outcome of cephaloceles is primarily related to the presence or absence of brain tissue inside the lesion. The largest available antenatal series reports a dismal prognosis for both varieties, with the possible exception of small lesions associated with normal intracranial anatomy.